We plan to determine if DNA containing base analogs such as bromouracil or aminopurine has altered sensitivity to bleomycin in vitro. If it does, we would then determine if the incorporation of these analogs into cellular DNA alters the sensitivity of bacterial and mammalian cells to bleomycin. We also plan to carry out measurements to characterize the DNA strand break produced by bleomycin. These may include: the change in number of breaks by treatment with alkali, acid and heat; characterization by treatment with various enzymes, of the end groups produced; release of compounds such as malonic aldehyde. If experiments on the differential release by bleomycin of the various DNA bases, now in progress at other labs, are incomplete, we will look at this area. These measurements will be done both in vitro and in vivo, where feasible, to give information on how the action of bleomycin on DNA in solution relates to its action in cells.